The early-stage triple-negative breast cancer landscape derives a novel prognostic signature and therapeutic target.

PURPOSE: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Patients with early-stage TNBCs have distinct likelihood of distant recurrence. This study aimed to develop a prognostic signature of early-stage TNBC patients to improve risk stratification. METHODS: Using RNA-sequencing data, we analyzed 189 pathologically confirmed pT1-2N0M0 TNBC patients and identified 21 mRNAs that were highly expressed in tumor and related to relapse-free survival. All-subset regression program was used for constructing a 7-mRNA signature in the training set (n = 159); the accuracy and prognostic value were then validated using an independent validation set (n = 158). RESULTS: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues. Early-stage TNBCs mainly consisted of basal-like immune-suppressed subtype and had higher homologous recombination deficiency scores. We developed a prognostic signature including seven mRNAs (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2). In both the training (n = 159) and validation set (n = 158), this signature could identify patients with relatively high recurrence risks and served as an independent prognostic factor. Time-dependent receiver operating curve showed that the signature had better prognostic value than traditional clinicopathological features in both sets. Functionally, we showed that TMEM101 promoted cell proliferation and migration in vitro, which represented a potential therapeutic target. CONCLUSIONS: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. This model may facilitate personalized therapy decision-making for early-stage TNBCs individuals.

Total laparoscopic segmental gastrectomy for gastrointestinal stromal tumors: A case report.

BACKGROUND: Gastrointestinal stromal tumors are lesions that originate from digestive tract walls. Several laparoscopic techniques, including local resections, wedge resections and partial gastrectomies, have been used successfully. However, there are no reports on laparoscopic segmental gastrectomy for gastrointestinal stromal tumors. CASE SUMMARY: We present our analysis of 17 patients who were admitted to our hospital from January 2014 to December 2018. All tumors were located in the corpus and antrum of the stomach, close to the lesser curvature of the stomach. The tumors originated from the anterior wall in nine cases and from the posterior wall of the stomach in eight cases. Laparoscopic segmental gastrectomy and end-to-end anastomosis between the proximal and the distal residual stomach were used in all patients. The mean operative time was 112.4 min. The mean length of hospital stay was 4.6 d. Mean operative blood loss was 73.5 mL. There were no leaks, no postoperative bleeding nor need for reintervention. Mean postoperative follow-up was 35.4 mo. The Visick grading index showed fewer gastrointestinal symptoms 3 mo after surgery. Two patients (11.8%) had reflux esophagitis and gastritis. CONCLUSION: Laparoscopic segmental gastrectomy may be a new function-preserving gastrectomy that is feasible for treatment of gastrointestinal stromal tumors that grow in the middle third of the stomach and on the lesser stomach curvature.

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies.

We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.

The endogenous retrovirus-derived long noncoding RNA TROJAN promotes triple-negative breast cancer progression via ZMYND8 degradation.

Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. Here, our genome-wide transcriptome analysis of HERVs revealed that a primate long noncoding RNA, which we dubbed TROJAN, was highly expressed in human triple-negative breast cancer (TNBC). TROJAN promoted TNBC proliferation and invasion and indicated poor patient outcomes. We further confirmed that TROJAN could bind to ZMYND8, a metastasis-repressing factor, and increase its degradation through the ubiquitin-proteasome pathway by repelling ZNF592. TROJAN also epigenetically up-regulated metastasis-related genes in multiple cell lines. Correlations between TROJAN and ZMYND8 were subsequently confirmed in clinical samples. Furthermore, our study verified that antisense oligonucleotide therapy targeting TROJAN substantially suppressed TNBC progression in vivo. In conclusion, the long noncoding RNA TROJAN promotes TNBC progression and serves as a potential therapeutic target.

Effects of adjuvant chemotherapy in T1N0M0 triple-negative breast cancer.

OBJECTIVES: Patients with T1N0M0 breast cancers are considered to have an excellent prognosis, even in triple-negative breast cancer (TNBC), which is often associated with diminished recurrence-free survival (RFS) and overall survival. Chemotherapy remains the only adjuvant treatment for TNBC, but evidence that adjuvant chemotherapy is beneficial for stage T1N0M0 TNBC patients is limited. In this study, we aimed to evaluate the effect of adjuvant chemotherapy and the benefit of taxanes in T1N0M0 TNBC patients. MATERIAL AND METHODS: A cohort of 354 consecutive patients with newly diagnosed T1N0M0 TNBC between January 2008 and December 2015 were included from the Fudan University Shanghai Cancer Center. Univariate and multivariate survival analyses were performed to compare patients treated with adjuvant chemotherapy with/without taxane addition. RESULTS: Median follow-up was 45 months. Chemotherapy was used in 92.4% of patients. The 5-year estimated RFS rates of patients with and without adjuvant chemotherapy were 94.5% and 83.6%, respectively. In multivariate analysis, adjuvant chemotherapy and a lack of lymphovascular invasion were associated with a significant benefit for RFS. A significant RFS benefit from adjuvant chemotherapy was observed in T1c (hazard ratio, HR = 0.24, 95% CI [0.08-0.76], P = 0.014) but not in T1b (HR = 0.32, 95% CI [0.03-3.18], P = 0.330) subgroups. Addition of taxane to an anthracycline-based regimen was not significantly associated with improved RFS in T1N0M0 TNBC patients. CONCLUSION: Adjuvant chemotherapy improves recurrence-free survival in T1c TNBC patients but not in T1b. Anthracycline-based taxane-free regimens might be sufficient to achieve RFS benefits in T1N0M0 TNBC patients.

[Treatment for severe rectal prolapse by laparoscopic rectopexy].

OBJECTIVE: To evaluate the clinical practice of laparoscopic rectopexy in the treatment of severe rectal prolapse. METHODS: From March 1998 to February 2007, 4 cases of complete rectal prolapse, including 1 male and 3 female,ranged 21-82 years old, were treated by laparoscopic rectopexy. In one case, the posterior wall of rectum was freed and elevated, and pre-rectal introcession was closed by silk suture, then the posterior wall was suspended and fixed on sacral promontory fascia, finally the sigmoid colon was fixed by sutures on the fascia of left psoas major. In other three cases, insertion of mesh was performed. Rectum was freed and elevated to the level of levalor ani. A sheet of T-shape polypropylene mesh was placed posterior to the rectum, whose lower margin was at the level of levator ani and wrapped around the rectum covering except the anterior wall. The free margin of the mesh was sutured on the muscular layer of rectum, then the mesh was put posterior to the rectum and fixed on the sacral promontory fascia by clipping to repair hernia. After that, the pelvic peritoneum was closed, and finally the sigmoid colon was fixed by sutures on the fascia of left psoas major. RESULTS: Four operation procedures were completed successfully. There was no conversion operation. The time was consumed 92.5 (80-100) min, and the bleeding amount was 6.5 (5-10) ml. No post-operative complications were found. Urine incontinence and encopresis were relieved. No recurrence and constipation was found after 2 months to 3 years follow up postoperatively. CONCLUSION: Laparoscopic rectopexy is a safe, workable and effective procedure, which can reduce operative trauma and shorten hospitalization time.